We concur with Smith and colleagues that evidence on harms for such therapies as GET for ME/CFS is insufficient (1, 2). Trials of GET for these conditions have focused on efficacy measures, which do not provide good information on whether adverse events occurred (2). A systematic review by Marques and associates assessed the reporting of “treatment side effects” in 16 randomized, controlled trials (3). Eleven were allocated the lowest mark, with only 1, the PACE trial, awarded the top mark (3, 4).

One randomized, controlled trial is generally seen as insufficient to make firm recommendations. Moreover, questions remain about the level of GET adherence in the PACE trial: The only reported measure of treatment adequacy was the number of appointments attended, not the type, intensity, or duration of activity/exercise performed each week. If participants dutifully adhered to the exercise program, one would not expect no improvement in fitness in the GET group as has been reported (4). If participants do not take their medication in a trial, it will not yield reliable information on safety; similarly, if participants do not adhere to an exercise regimen, good information will not be obtained about the safety or harms of adhering to the intervention. A previous review of 3 trials of graded activity–oriented interventions for CFS found that, after treatment, intervention participants had not actually increased their activity levels (objectively measured using actometers) compared with control participants (5).